SYNTHESIS AND FKBP BINDING OF SMALL-MOLECULE MIMICS OF THE TRICARBONYL REGION OF FK506

Authors
WANG GT LANE B FESIK SW PETROS A LULY J KRAFFT GA
Citation
Gt. Wang et al., SYNTHESIS AND FKBP BINDING OF SMALL-MOLECULE MIMICS OF THE TRICARBONYL REGION OF FK506, Bioorganic & medicinal chemistry letters, 4(9), 1994, pp. 1161-1166
Citations number
21
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
4
Issue
9
Year of publication
1994
Pages
1161 - 1166
Database
ISI
SICI code
0960-894X(1994)4:9<1161:SAFBOS>2.0.ZU;2-W
Abstract
Small acyclic model compounds were synthesized to examine the importan ce of the C(9) carbonyl group of FK506 for FKBP binding. 4-(4'-Methoxy phenyl)-1-butyl (3'', 4'', 5''-trimethoxyphenylglyoxyl) pipecolate (co mpound 2d), containing the N-(glyoxyl)pipecolate motif of FK506, was f ound to bind to FKBP with IC50 of 16 mu M. Replacement of the carbonyl group at the position corresponding to C(9) of FK506 with small nonpo lar groups (hydrogen, methylene or methyl group, compounds 2a-2c) sign ificantly reduced the binding affinity.